title: Cytosolic phosphorylated EGFR is predictive of recurrence in early stage penile cancer patients: a retropective study.
abstract: BACKGROUND
  Penile cancer (PC) is a rare tumor, and therapeutic options are limited for this disease, with an overall 5-year overall survival around 65-70%. Adjuvant therapy is not recommended for patients with N0-1 disease, despite up to 60% of these patients will die within 5 years from diagnosis.
  
  
  METHODS
  Medical records of all patients who underwent radical surgery at University Federico II of Naples and at National Tumor Institute "Pascale" of Naples for early squamous cell carcinoma of the penis from January, 2000 to December, 2011 were retrieved. Paraffin wax embedded tissue specimens were retrieved from the pathology archives of the participating Institutions for all patients. Expression of p-EGFR, EGFR and positivity to HPV were evaluated along with other histological variables of interest. Demographic data of eligible patients were retrieved along with clinical characteristics such as type of surgical operation, time of follow up, time of recurrence, overall survival. A multivariable model was constructed using a forward stepwise selection procedure.
  
  
  RESULTS
  Thirty eligible patients were identified. All patients were positive for EGFR by immunohistochemistry, while 13 and 16 were respectively positive for nuclear and cytosolic p-EGFR. No EGFR amplification was detected by FISH. Eight patients were positive for high-risk HPV by ISH. On univariable analysis, corpora cavernosa infiltration (OR 7.8; 95% CI=0,8 to 75,6; P=0,039) and positivity for cytosolic p-EGFR (OR 7.6; 95% CI =1.49 to 50; P = 0.009) were predictive for recurrence, while only positivity for cytosolic p-EGFR (HR =9.0; 95% CI 1.0-100; P=0,0116) was prognostic for poor survival.
  
  
  CONCLUSIONS
  It is of primary importance to identify patients with N0-1 disease who are at increased risk of recurrence, as they do not normally receive any adjuvant therapy. Expression of p-EGFR was found in this series to be strongly related to increase risk of recurrence and shorter overall survival. This finding is consistent with the role of p-EGFR in other solid malignancies. Integration of p-EGFR with classic prognostic factors and other histology markers should be pursued to establish optimal adjuvant therapy for N0-1 PC patients.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Lorenzo
authors.forename: Sisto
authors.initials: S
authors.lastname: Perdonà
authors.forename: Carlo
authors.initials: C
authors.lastname: Buonerba
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Gigantino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pannone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Quarto
authors.forename: Matteo
authors.initials: M
authors.lastname: Ferro
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gaudioso
authors.forename: Daniela
authors.initials: D
authors.lastname: Terracciano
authors.forename: Rossella
authors.initials: R
authors.lastname: Di Trolio
authors.forename: Pasquale
authors.initials: P
authors.lastname: Rescigno
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.forename: Sabino
authors.initials: S
authors.lastname: De Placido
authors.forename: Gaetano
authors.initials: G
authors.lastname: Facchini
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Ascierto
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
mesh_terms: D000368:Aged; D003600:Cytosol / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D009367:Neoplasm Staging; D010412:Penile Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D010766:Phosphorylation; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors